Transcription factors play a central role in the expression of specific genes upon stimulation by extracellular signals, thereby regulating a complex array of biological processes. Activator protein 1 (AP-1), also termed “activating protein 1,” “activation protein 1,” or “AP-1 transcription factor,” is a heterogenous mixture of heterodimers of several related protein subunits (Kodonaga and Tijan, Proc. Natl. Acad. Sci. USA, 83, 5889-5893, 1986). One notable member of the AP-1 family is the heterodimer formed of c-Fos and c-Jun. These two proteins are products of the c-fos and c-jun proto-oncogenes, respectively. Other subunits of AP-1 family include FosB, Fra-1, Fra-2, c-Jun, JunB, JunD, etc. (see, e.g., The FOS and JUN Families of Proteins, Angel and Herrlich, eds., CRC Press, Boca Raton, Fla., 1994; and SteinmÃller et al., Biochem J, 360: 599-607, 2001).
AP-1 has been implicated in abnormal cell proliferation and tumor formation. Members of AP-1 family alter gene expression in response to growth factors, cytokines, tumor promoters, carcinogens and increased expression of certain oncogenes. AP-1 proteins are expressed by lymphoid cells, and bind to effector cells such as macrophages and mast cells. In particular, the AP-1 proteins induce macrophage phagocytosis, expression of class II major histocompatibility molecules, cytotoxicity, and migration, and induce hematopoietic progenitor cell differentiation.
Modulation of AP-1 transcription factor activities or cellular levels would affect various cellular processes and provide therapeutic means for treating a number of diseases and conditions. There is a need in the art for novel methods and compositions for modulating AP-1 transcription factor activities and thereby inhibiting cell proliferation in tumor formation and tumor growth. The instant invention fulfills this and other needs.